Nonadherence to Imatinib adversely affects event free survival in chronic phase chronic myeloid leukemia

Abstract

There is limited data on the impact of treatment interruptions due to nonadherence in patients with chronic phase chronic myeloid leukemia (CP-CML) treated with Imatinib. We looked at factors (including adherence to therapy) affecting the outcome in a large cohort of patients with CP-CML. All the 516 patients received Imatinib free-of-cost through a company sponsored scheme, which mandated regular three monthly visits for drug procurement. Data regarding the disease characteristics, adherence to treatment and outcomes, were obtained from patients records. Unwarranted interruption of treatment for more than 1 week was defined as nonadherence. With a median follow-up of 39 months, the estimated 5-year event free survival (EFS) was 70.8% (95%, CI 5 63.3-78.3). Nearly one-third of the patients (29.6%) were found to be nonadherent at some point during their treatment. On univariate analysis, the factors adversely affecting the EFS were prolonged symptom duration before diagnosis, treatment with hydroxyurea for more than 1 month before start of Imatinib, and nonadherence to therapy. Only nonadherence was significant in multivariate analysis (HR1.6; P 5 0.048). The 5-year EFS in adherent and nonadherent patients was 76.7% and 59.8% respectively (P 5 0.011, log rank test). Nonadherent patients were less likely to achieve complete cytogenetic responses (26% versus 44%; P 5 0.004; v 2 test) at any point. A significant proportion of patients with CP-CML have drug interruptions due to nonadherence during therapy and this compromises the EFS. Adherence to therapy must be included as an important evaluation parameter in all future studies of CML. Am. J. Hematol. 86:471-474, 2011. V

Measurement of adherence to BCR-ABL inhibitor therapy in chronic myeloid leukemia: current situation and future challenges

“…Eight publications came from Europe, 14,15,18,19,21,24,25,30 5 from the US, 20,23,[31][32][33] 5 from Asia 22,26,28,29,35 and one from Australia.…”

“…An overview of the included articles is given in Online Supplementary Table S3. 14,15, Only 19 peer review articles were analyzed and reported in the Results section.Eight publications came from Europe, 14,15,18,19,21,24,25,30 5 from the US, 20,23,[31][32][33] 5 from Asia 22,26,28,29,35 and one from Australia.27 Almost half of the included studies were retrospective (9 of 19) and mainly conducted in the US and Asia 38,41,42,45,49,52,53 while half of the European studies were prospective (4 of 8). 14,15,18,24 …”

“…a patient was non-adherent if intake was less than 80-90% of total medication) and measured by MEMS ® , MPR, or questionnaire, 3-56% of patients were classified as non-adherent (Figure 4). 14,15,[22][23][24][25]32,34 …”

“…Two recent studies confirmed the poor impact of suboptimal adherence on clinical outcomes ( Figure 5B). 22,24 No studies were identified in the literature review that investigated the impact of non-adherence on overall survival, safety, quality of life (QoL) or other patient reported outcomes.However, 3 studies showed adherence impacted negatively on resource utilization and costs. All were USA retrospective claims database studies measuring adherence with MPR.…”

Patient adherence to tyrosine kinase inhibitor therapy in chronic myeloid leukemia

“…Recently, a third study, performed at the Adyar Cancer Institute, Chennai, India, has been reported in the literature [20]. The authors evaluated the records of 516 patients receiving imatinib for chronic-phase CML for adherence to therapy and patient outcomes.…”